The long term goals of this project are to delineate changes in neural control of the HPA axis which occur with chronic stress and to determine how these changes affect physiology and behavior. Chronic stress causes facilitated behavioral, sympathetic (SNS) and HPA responses to new stressors. Delineation of the mechanism(s) underlying these changes will apply directly to understanding of the major societal problem of chronic stress disorders, e.g., depression, PTSD, etc. Moreover, chronic stress has been suggested to cause preferential abdominal obesity, associated with NIDDM, CAD and stroke. Three characteristics of facilitated acute responses in chronically stressed rats must be explained by the neural circuit that mediates them: facilitation occurs in the AM, not the PM; as steady-state corticosterone (B) increases in stressed rats so does facilitation; and, SNS and behavioral responses are also facilitated in chronically stressed rats. The number of c-fos staining (active) neurons increases in 4 brain sites after acute stress in chronically stressed cf. naive rats: in midline thalamus (which received major circadian input from the suprachiasmatic nuclei and projects to), the amygdala (which project to) both neuroendocrine cells of the parvocelular paraventricular (PVN) hypothalamus and to central SNS nuclei. Three aims test whether: (1) the thalamic paraventricular nucleus (PVTh) controls diurnal facilitation and sends this information preferentially to the amygdala; (2) the amygdala, specifically corticotropin releasing factor (CRF) cells, execute facilitated responses in the HPA axis and the SNS; and (3) these extrahypothalamic cell groups alter function in medial hypothalamic nuclei that regulate energy balance during chronic stress. Methods to be used include: c-fos mRNA to follow facilitation after acute stress in chronically stressed rats; lesions to block facilitation in specific neural sites; beta implants over amygdala to determine the effect of the steroid on CRF; selected neropeptides and receptors measured by semiquantitative mRNA analysis. Food intake, body weight, plasma hormones and temperature, plasma metabolites and the activity in white and brown fat depots will be measured for HPA and SNS responsitivity and determination of changes in energy balance. If the underlying hypotheses are correct, these experiments will provide evidence that the basis neural circuit that mediates facilitated stress responses in chronically stressed rats is part of the "conditioned fear response" circuit.